非小细胞肺癌浅表转移淋巴结EGFR基因状态及EGFR-TKI疗效分析
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摘要
目的:分析非小细胞肺癌(NSCLC)患者浅表淋巴结EGFR基因突变状态及其采用EGFR-TKI治疗的效果。方法:选取经病理确诊为NSCLC转移浅表淋巴结及部分配对肿瘤原发灶石蜡组织标本行EGFR基因检测,分析临床病理资料,比较部分病例浅表淋巴结转移灶与肿瘤原发灶EGFR基因突变状态差异。此外,根据检测结果分组,比较各组的PFS,并采用COX回归分析了解PFS的影响因素。结果:56例浅表淋巴结行EGFR检测,35例EGFR突变阳性与EGFR野生型21例。无吸烟、腺癌与EGFR突变相关,而女性突变率高于男性,但差异无统计学意义(P>0.05)。11例淋巴结与配对肿瘤原发灶一致性分析,两者一致率为81.8%,Kappa值为0.645,P值为0.020。35例EGFR突变阳性者采用EGFR-TKI治疗,其PFS优于21例采用化疗的EGFR野生型组。COX多因素回归显示,校正腺癌、PS评分,EGFR突变阳性者有利于延长PFS。结论:非小细胞肺癌浅表转移淋巴结EGFR突变检测可用于指导EGFR-TKI的使用。
Objective Analysis of EGFR gene mutation status in superficial lymph nodes of NSCLC patients and its therapeutic effect with EGFR-TKI.Method Pathologically confirmed superficial lymph nodes with NSCLC metastasis and paraffin tissue specimens of some primary tumors were examined for EGFR gene.The clinical and pathological data were analyzed and the differences of EGFR gene mutation between superficial lymph node metastases and primary tumors in some cases were compared.In addition,according to the test results,the PFS of each group was compared,and the influencing factors of PFS were analyzed by COX regression.Results 56 cases of superficial lymph nodes underwent EGFR detection,35 cases of EGFR mutation and 21 cases of EGFR wild type.Non-smoking and adenocarcinoma were associated with EGFR mutation,while the mutation rate in women was higher than that in men,but there was no significant difference(P>0.05).The consistency between lymph nodes and matched primary tumors was 81.8%,Kappa value was 0.645 and P value was 0.020.35 cases of EGFR mutation positive were treated with EGFR-TKI,and their PFS was better than 21 cases of EGFR wild type group treated with chemotherapy.COX multivariate regression showed that correction of adenocarcinoma,PS score and EGFR mutation were beneficial to PFS extension.Conclusion The EGFR gene status of superficial metastasis lymph node can be a good guidance for NSCLC patients treated by EGFR-TKI.
Objective Analysis of EGFR gene mutation status in superficial lymph nodes of NSCLC patients and its therapeutic effect with EGFR-TKI.Method Pathologically confirmed superficial lymph nodes with NSCLC metastasis and paraffin tissue specimens of some primary tumors were examined for EGFR gene.The clinical and pathological data were analyzed and the differences of EGFR gene mutation between superficial lymph node metastases and primary tumors in some cases were compared.In addition,according to the test results,the PFS of each group was compared,and the influencing factors of PFS were analyzed by COX regression.Results 56 cases of superficial lymph nodes underwent EGFR detection,35 cases of EGFR mutation and 21 cases of EGFR wild type.Non-smoking and adenocarcinoma were associated with EGFR mutation,while the mutation rate in women was higher than that in men,but there was no significant difference(P>0.05).The consistency between lymph nodes and matched primary tumors was 81.8%,Kappa value was 0.645 and P value was 0.020.35 cases of EGFR mutation positive were treated with EGFR-TKI,and their PFS was better than 21 cases of EGFR wild type group treated with chemotherapy.COX multivariate regression showed that correction of adenocarcinoma,PS score and EGFR mutation were beneficial to PFS extension.Conclusion The EGFR gene status of superficial metastasis lymph node can be a good guidance for NSCLC patients treated by EGFR-TKI.
引文
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[22] 陈惠,王汉萍,张力,等.盐酸埃克替尼一线治疗晚期非小细胞肺癌的疗效与安全性[J].中华内科杂志,2017,(1):39.
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[25] Z L,Y Z,W B,et al.Insufficiency of peripheral blood as a substitute tissue for detecting EGFR mutations in lung cancer:a meta-analysis[J].Targeted Oncology,2014,9(4):381.
[2] 石远凯,孙燕,丁翠敏,等.中国埃克替尼治疗非小细胞肺癌专家共识(2016年版)[J].中国肺癌杂志,2016,19(7):489.
[3] Bell D W,Lynch T J,Haserlat S M,et al.Epidermal growth factor receptor mutations and gene amplification in non-small-cell lung cancer:molecular analysis of the IDEAL/INTACT gefitinib trials[J].China Prescription Drug,2005,23(31):8081.
[4] 欧阳玉秀,叶奕菁,徐智健,等.肺癌的锁骨上淋巴结转移特点及靶区勾画建议[J].临床肺科杂志,2016,21(4):643.
[5] Lee D H,Yoon T M,Lee J K,et al.Supraclavicular Lymph Node Excision Biopsy in Patients with Suspected Supraclavicular Lymph Node Metastasis of Lung Cancer:Experience in a Tertiary Hospital[J].Chonnam Medical Journal,2017,53(1):69.
[6] 中国非小细胞肺癌患者表皮生长因子受体基因突变检测专家组.中国非小细胞肺癌患者表皮生长因子受体基因突变检测专家共识(2016版)[J].中华病理学杂志,2016,45(4):217.
[7] Gao B,Sun Y,Zhang J,et al.Spectrum of LKB1,EGFR,and KRAS Mutations in Chinese Lung Adenocarcinomas[J].Journal of Thoracic Oncology,2010,5(8):1130.
[8] Chao L,Yisheng H,Yu C,et al.Relevance of EGFR mutation with micropapillary pattern according to the novel IASLC/ATS/ERS lung adenocarcinoma classification and correlation with prognosis in Chinese patients[J].Lung Cancer,2014,86(2):164.
[9] 韦丽丽,李幸洲,于忠和.非小细胞肺癌患者浅表淋巴结组织中表皮生长因子受体基因和EML4-ALK融合基因的突变状态[J].中华医学杂志,2015,95(26):2070.
[10] 冷再君,徐傲,徐修才,等.多途径标本检测NSCLC患者EGFR基因突变[J].安徽医科大学学报,2014,49(9):1320.
[11] Zhang Y,Sun Y,Pan Y,et al.Frequency of driver mutations in lung adenocarcinoma from female never-smokers varies with histologic subtypes and age at diagnosis[J].Clinical Cancer Research,2012,18(7):1947.
[12] Satouchi M,Mitsudomi T,Ebi N,et al.A PHASE III TRIAL OF GEFITINIB VERSUS CISPLATIN/DOCETAXEL FOR NSCLC PATIENTS WITH ACTIVATING EGFR MUTATION;WJTOG 3405[J].Annals of Oncology,2010:11.
[13] Gridelli C,Rossi A.EURTAC first-line phase III randomized study in advanced non-small cell lung cancer:Erlotinib works also in European population[J].Journal of Thoracic Disease,2012,4(2):219.
[14] Lie C H,Chang H C,Chao T Y,et al.First- or second-line gefitinib therapy in unknown epidermal growth factor receptor mutants of non-small-cell lung cancer patients treated in Taiwan[J].Clinical Lung Cancer,2011,12(2):116.
[15] 卿松,刘铭,师艺,等.表皮生长因子受体基因在非小细胞肺癌原发灶与淋巴结转移灶中的突变情况分析及临床意义[J].中国医药导报,2015,12(21):21.
[16] Gow C H,Chang Y L,Hsu Y C,et al.Comparison of epidermal growth factor receptor mutations between primary and corresponding metastatic tumors in tyrosine kinase inhibitor-naive non-small-cell lung cancer[J].Annals of Oncology Official Journal of the European Society for Medical Oncology,2009,20(4):696.
[17] Suda K,Murakami I,Hui Y,et al.Heterogeneity of EGFR Aberrations and Correlation with Histological Structures:Analyses of Therapy-Naive Isogenic Lung Cancer Lesions with EGFR Mutation[J].Journal of Thoracic Oncology,2016,11(10):1711.
[18] Schmid K,Oehl N F.EGFR/KRAS/BRAF mutations in primary lung adenocarcinomas and corresponding locoregional lymph node metastases[J].Clinical Cancer Research An Official Journal of the American Association for Cancer Research,2009,15(14):4554.
[19] Wang F,Fang P,Hou D Y,et al.Comparison of epidermal growth factor receptor mutations between primary tumors and lymph nodes in non-small cell lung cancer:a review and meta-analysis of published data[J].Asian Pac J Cancer Prev,2014,15(11):4493.
[20] Molina J R,Yang P,Cassivi S D,et al.Non-Small Cell Lung Cancer:Epidemiology,Risk Factors,Treatment,and Survivorship[J].Mayo Clinic Proceedings,2008,83(5):584.
[21] 许荣,崔腾斌,张春荣.顺铂分别联合培美曲塞与多西他赛治疗晚期肺腺癌的临床观察与分析[J].吉林医学,2014,35(27):6017.
[22] 陈惠,王汉萍,张力,等.盐酸埃克替尼一线治疗晚期非小细胞肺癌的疗效与安全性[J].中华内科杂志,2017,(1):39.
[23] Mok T S,Wu Y L,Thongprasert S,et al.Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma[J].The Journal of Evidence-Based Medicine,2009,361(10):947.
[24] Massuti B,Morán T,Porta R,et al.Multicenter prospective trial of customized erlotinib for advanced non-small cell lung cancer (NSCLC) patients (p) with epidermal growth factor receptor (EGFR) mutations:Final results of the Spanish Lung Cancer Group (SLCG) trial[J].Journal of Clinical Oncology,2009.
[25] Z L,Y Z,W B,et al.Insufficiency of peripheral blood as a substitute tissue for detecting EGFR mutations in lung cancer:a meta-analysis[J].Targeted Oncology,2014,9(4):381.